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Sick animals have long been recognized by farmers as having different behavior. Initially it was thought that this was due to physical weakness that resulted from diverting energy from the body processes needed to fight infection. However, in the 1960s, it was shown that animals produced a blood carried ‘‘factor X’’ that acted upon the brain to cause this such sickness behavior.[10][11] In 1987, Benjamin L. Hart brought together a variety of research findings that argued for them being survival adaptations that if prevented would disadvantage an animal’s ability to fight infection. In the 1980s, the blood borne factor was shown to be proinflammatory cytokines produced by activated leukocytes in the immune system in response to lipopolysaccharides (a cell wall component of Gram-negative bacteria). These cytockines acted by various humeral and nerve routes upon the hypothalmus and other areas of the brain. Further research showed that the brain can also learn to control the various components of sickness behavior independently of immune activation.

Sickness behavior in its different aspects cauess an animal to limit its movement and so reduce its energy expenditure allowing this to be diverted to mobilize the fever response which involves raising body temperature.[1] They also limits an animal’s exposure to predators while it is cognitively and physically impaired.[1]

The individual components of sickness behavior have specific individual advantages. Anorexia limits the ingestion of foods and so the availability in the gut and from gut absorption of iron and zinc that might aid bacterial reproduction.[12] Plasma concentrations of iron and zinc are lowered for this reason in fever.[13]Lowered threshold for pain ensures that an animal is attentive that it does not place pressure of injuried and inflammed tissues that might disrupt their healing.[1] Reduced grooming is adaptive since it reduces water loss.[1]

The components of behavioral sickness can be learnt by conditional association such that if say a saccharin solution is given with a chemical that triggers a particular aspect of sickness behavior that on later occasions the saccharin solution will trigger it by itself.[22][23]

It has been proposed that major depressive disorder is near-identical with sickness behavior so raising the possibility that is a maladaptive manifestation of sickness behavior due to abnormalities in circulating cytokines.[24][25]